A micro-sized headspace GC technique for determination of organic volatileimpurities in water-insoluble pharmaceuticals

A micro-sized headspace technique is presented for determination of organic volatile impurities (OVIs) in water-insoluble pharmaceuticals. Its main fe atures include reduction of the amounts of sample of drug and sample dissol ution medium, from 100 - 200 mg and 1 - 5 mL, respectively, in the traditio nal headspace method to 5 - 30 mg and 100 muL in the micro-sized headspace method, and shortening the headspace equilibration time from 45 - 60 min to 5 - 10 min. The validity of method has been examined both experimentally and theoretica lly. The relative standard deviation of the analysis and the linearity of m ethod satisfied the requirements of the United States Pharmacopoeia. It was found that headspace equilibrium conditions have little influence on the s ensitivity of the method, and that the presence of different amounts of dru g substance in the sampling solution has little effect on the analytical re sults, in contrast with the traditional headspace GC method.